Although hematopoietic stem cell transplantation (HSCT) has been used for the treatment of AML for nearly thirty years, relapse of disease and transplant-related mortality remain high. In an effort to decrease relapse without increasing toxicity, targeted radiotherapy using iodine-131 (131 I) conjugated to an antibody (BC8) directed against the panhematopoietic antigen CD45 has been used to deliver higher doses of radiation to bone marrow and other sites of leukemic involvement. To date, 131 I-BC8 antibody has been combined with conventional HSCT preparative regimens, including cyclophosphamide (CY) and 12 Gy TBI in a Phase I study for patients with advanced acute leukemia, and busulfan (BU)/CY in patients with AML in first CR. These combined regimens have been well-tolerated and have demonstrated low relapse rates to date, and thus, we propose clinical studies to determine whether the addition of targeted hematopoietic irradiation to conventional preparative regimens can improve disease-free survival by decreasing relapse without excessive regimen-related toxicity. Our goals include completing a Phase II study of 131 I-antibody followed by BU/CY in patients with AML in first CR, initiating a multi-institutional Phase III trial comparing this regimen to BU/CY alone, and completing a Phase II study of 1311-antibody followed by CY/12 Gy TBI in patients with advanced AML. However, the addition of targeted radiation to full-dose conventional preparative regimens has not served to decrease the overall toxicity of HSCT. Recent experience conditioning patients with a non-myeloablative regimen of 2 Gy TBI and the immunesuppressive agents cyclosporine and mycophenolate mofetil has demonstrated that partial to complete donor chimerism can be achieved with the infusion of G-CSF-stimulated peripheral blood stem cells from HLA-matched related or unrelated donors. Thus, for older patients with advanced AML who would not tolerate a conventional transplant, we will conduct a Phase I study to determine the maximum tolerated dose of radiation delivered by 131 I- antibody which can be combined with this non-myeloablative regimen. Targeted radiation should decrease the leukemic cell bulk in order to optimize the chance that the graft versus leukemia effect provided by engrafted donor cells can eradicate disease.